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CpG increases vaccine antigen-specific cell-mediated immunity when administered with hepatitis B vaccine in HIV infection.

Angel JB, Cooper CL, Clinch J, Young CD, Chenier A, Parato KG, Lautru M, Davis H, Cameron DW - J Immune Based Ther Vaccines (2008)

Bottom Line: Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination.Similar results were observed when LPR were evaluated as stimulation indices (SI).This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ottawa Health Research Institute, 501 Smyth Rd,, Ottawa, ON, K1H 8L6, Canada. jangel@ohri.ca.

ABSTRACT

Background: Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpGs are potent vaccine adjuvants and may be an important component of the development vaccines, particularly those for which a cellular immune response is required for protection. We have previously demonstrated that CpG ODN co-administration with hepatitis B vaccine results in earlier, stronger and more sustained antibody responses to hepatitis B surface antigen in HIV infected individuals, and wished to determine if, in this population, helper T-cell responses were also enhanced.

Methods: We conducted a double-blind, placebo-controlled trial in hepatitis B susceptible, effectively treated HIV-seropositive individuals. Participants received hepatitis B vaccine, with either placebo or CPG 7909 1.0 mg at week 0, 4 and 8. To determine the impact of CpG on cellular immune responses, lymphoproliferative responses (LPR) were evaluated by [3H]-thymidine incorporation at baseline and weeks 4, 8, 12, 24, and 48. Immunophenotyping of lymphocyte subsets was also determined at these time points.

Results: Of 36 patients enrolled, 18 received hepatitis B vaccine alone, and 18 received hepatitis B vaccine with CpG. Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination. This increase was statistically significant at 8 weeks (p = 0.042) and 48 weeks (p = 0.024). Similar results were observed when LPR were evaluated as stimulation indices (SI). No differences in proliferative responses to HIV p24 Ag were observed, nor were there any differences in lymphocyte subsets.

Conclusion: In addition to enhancing humoral responses to vaccination, we describe for the first time that CPG 7909 enhances cellular immunity to vaccine antigen in a typically hyporesponsive population. This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.

No MeSH data available.


Related in: MedlinePlus

Proliferative responses to hepatitis B surface antigen (HBsAg). A) stimulation index (SI) or B) change in SI from baseline are enhanced over the 48 week study period in subjects that received hepatitis B vaccine plus CpG (solid line; n = 19) as compare to those that received hepatitis B vaccine alone (broken line (n = 19) *p 0.04 by Mann Whitney U Test.
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Figure 2: Proliferative responses to hepatitis B surface antigen (HBsAg). A) stimulation index (SI) or B) change in SI from baseline are enhanced over the 48 week study period in subjects that received hepatitis B vaccine plus CpG (solid line; n = 19) as compare to those that received hepatitis B vaccine alone (broken line (n = 19) *p 0.04 by Mann Whitney U Test.

Mentions: Helper T cell responses over the 48-week study period, as evaluated by lymphoproliferation (expressed as cpm) in response to ex vivo stimulation with HBsAg were significantly greater at all time points from 4 weeks onward in subjects receiving CPG 7909 compared to control subjects receiving Engerix-B alone (Figure 1). Proliferative responses were also evaluated by stimulation index (SI), as well as a change in SI from baseline (Figure 2A, B). Consistent with that observed with cpm, the inclusion of CPG 7909 also resulted in greater proliferative responses and greater increases in proliferative response from baseline. Using an SI of 5 at week 48 to define a positive proliferative response to HBsAg, there were 8 responders of 19 subjects (42%) in the group that received CPG 7909 compared to only 3 of 19 (16%) in the control group (p = 0.07 by Chi square test). The mean SI of these responders was 17.3 in the CpG group and 8.3 in the control group.


CpG increases vaccine antigen-specific cell-mediated immunity when administered with hepatitis B vaccine in HIV infection.

Angel JB, Cooper CL, Clinch J, Young CD, Chenier A, Parato KG, Lautru M, Davis H, Cameron DW - J Immune Based Ther Vaccines (2008)

Proliferative responses to hepatitis B surface antigen (HBsAg). A) stimulation index (SI) or B) change in SI from baseline are enhanced over the 48 week study period in subjects that received hepatitis B vaccine plus CpG (solid line; n = 19) as compare to those that received hepatitis B vaccine alone (broken line (n = 19) *p 0.04 by Mann Whitney U Test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2526993&req=5

Figure 2: Proliferative responses to hepatitis B surface antigen (HBsAg). A) stimulation index (SI) or B) change in SI from baseline are enhanced over the 48 week study period in subjects that received hepatitis B vaccine plus CpG (solid line; n = 19) as compare to those that received hepatitis B vaccine alone (broken line (n = 19) *p 0.04 by Mann Whitney U Test.
Mentions: Helper T cell responses over the 48-week study period, as evaluated by lymphoproliferation (expressed as cpm) in response to ex vivo stimulation with HBsAg were significantly greater at all time points from 4 weeks onward in subjects receiving CPG 7909 compared to control subjects receiving Engerix-B alone (Figure 1). Proliferative responses were also evaluated by stimulation index (SI), as well as a change in SI from baseline (Figure 2A, B). Consistent with that observed with cpm, the inclusion of CPG 7909 also resulted in greater proliferative responses and greater increases in proliferative response from baseline. Using an SI of 5 at week 48 to define a positive proliferative response to HBsAg, there were 8 responders of 19 subjects (42%) in the group that received CPG 7909 compared to only 3 of 19 (16%) in the control group (p = 0.07 by Chi square test). The mean SI of these responders was 17.3 in the CpG group and 8.3 in the control group.

Bottom Line: Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination.Similar results were observed when LPR were evaluated as stimulation indices (SI).This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ottawa Health Research Institute, 501 Smyth Rd,, Ottawa, ON, K1H 8L6, Canada. jangel@ohri.ca.

ABSTRACT

Background: Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpGs are potent vaccine adjuvants and may be an important component of the development vaccines, particularly those for which a cellular immune response is required for protection. We have previously demonstrated that CpG ODN co-administration with hepatitis B vaccine results in earlier, stronger and more sustained antibody responses to hepatitis B surface antigen in HIV infected individuals, and wished to determine if, in this population, helper T-cell responses were also enhanced.

Methods: We conducted a double-blind, placebo-controlled trial in hepatitis B susceptible, effectively treated HIV-seropositive individuals. Participants received hepatitis B vaccine, with either placebo or CPG 7909 1.0 mg at week 0, 4 and 8. To determine the impact of CpG on cellular immune responses, lymphoproliferative responses (LPR) were evaluated by [3H]-thymidine incorporation at baseline and weeks 4, 8, 12, 24, and 48. Immunophenotyping of lymphocyte subsets was also determined at these time points.

Results: Of 36 patients enrolled, 18 received hepatitis B vaccine alone, and 18 received hepatitis B vaccine with CpG. Inclusion of CPG 7909 was associated with a greater proliferative response to HBsAg at all time points following initial vaccination. This increase was statistically significant at 8 weeks (p = 0.042) and 48 weeks (p = 0.024). Similar results were observed when LPR were evaluated as stimulation indices (SI). No differences in proliferative responses to HIV p24 Ag were observed, nor were there any differences in lymphocyte subsets.

Conclusion: In addition to enhancing humoral responses to vaccination, we describe for the first time that CPG 7909 enhances cellular immunity to vaccine antigen in a typically hyporesponsive population. This adjuvancy may be important in the development of an effective vaccine for which a cellular immune response is required for protection.

No MeSH data available.


Related in: MedlinePlus